Defining and Regulating Combination Products: An Evolutionary Journey

Chapter 1: Introduction – Key Considerations Advanced by this Handbook

In this episode of The Combination Products Handbook: The Series, host Tom von Gunden discusses Chapter 1 of The Combination Products Handbook: A Practical Guide for Combination Products and Other Combined Use Systems (CRC Press, 2023) with the book’s editor, Susan Neadle. Given that the initial chapter was penned by the FDA’s John “Barr” Weiner, the discussion focuses on reasons for establishing the historical and regulatory context for combination products early in the handbook’s topic coverage.

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The Combination Products Handbook: A Practical Guide for Combination Products and Other Combined Use Systems Edited by Susan W.B. Neadle, CRC Press, 2023

Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of The Combination Products Handbook: The Series, a series in which we will take The Combination Products Handbook: A Practical Guide, published by CRC Press in 2023, through a chapter-by-chapter discussion. My name is Tom von Gunden, Chief Editor and Community Director at Drug Delivery Leader, and I will be the host for the series. Today, in a discussion of Chapter 1, I am joined by the book’s editor and, for some chapters, author or coauthor, Susan Neadle.

Welcome, Susan.

Susan Neadle:

Thanks for having me.

Susan, you and I are here today to talk about Chapter 1 of the book, “Key Considerations Advanced by this Handbook.” We know that it was penned by John “Barr” Weiner from the FDA. Folks in the audience, I have a separate interview with Barr in a series on Drug Delivery Leader called Sit and Deliver, which I certainly encourage you to check out. We talk about various things, including some of the commentary he put into The Combination Products Handbook. But, Susan, from your perspective as the editor and one of the authors of the book, why was it important to have the FDA perspective and, especially, why establish that perspective right out of the gate in Chapter 1?

Going into writing this book and recognizing that I wanted it to cover the full life cycle of combination products, I recognized that the FDA has created the most mature combination product regulatory framework globally. Getting their perspective on the history behind creating it and how they aligned was important to me. I reached out to Barr and asked him if he'd be willing to participate in either reviewing or writing anything in the book, and in an unofficial capacity, he agreed.

He said that the framework for combination products is fairly mature at this point compared to where it was so many years ago, and that he’d been on this journey with the FDA as the regulatory framework was being built. Barr was a core individual who participated in that building. Reaching out to him, getting his perspective, his alignment, and [his confirmation] that it was a good time to put out a work like this reaffirmed why I was going after it and what I was doing.

Susan, if you could comment on the regulatory landscape in the industry, what does that evolution and trajectory look like to you in terms of the things that Barr covered in Chapter 1, and the way it looks to you from your experience?

From my experience, I look back to the early 2000s when there was a global issue with people making changes to syringes and not necessarily paying attention to the system as a whole. They were just thinking, Well, it's the drug. The only thing that matters is the drug. If I make a change to the device, what's the big deal? Taking a giant step back and looking at the journey that the FDA has been on with industry, we've really come a long way. When you read through the history that Barr walks through in the chapter, [including] the initial congressional efforts in the U.S., and then moving forward into defining combination products as a clear class of products, [it was being driven by] this whole mindset of risk-based, systemic thinking: thinking comprehensively about planning, analyzing, and thinking about the product as a whole. That is critical to combination products and driving safety and efficacy for combined use.

The concepts that Barr introduced [in Chapter 1] and that the industry has gone through in the ongoing development of regulatory programs, framework, guidance, and best practices about what works best, have all matured to a point where people are starting to recognize some common themes. [That includes] how important it is to collaborate, the partnership with suppliers, working across boundaries, and not operating in silos. You've got to work across the boundaries of who's the drug person and who's the device person? Oh, wait, we're in it together. [That also means] getting past misinterpretation due to language barriers. The book and Barr's chapter, which reflects on the journey that we've been on, is a manifestation of the whole vision of how we can pull it together to make products safer and more effective for the industry globally by applying these risk-based concepts.

Chapter 1 does a solid job of tracing the evolution of the regulatory framework for combination products in the U.S. From your perspective, what's next?

It's continuing to drive people to this shared vision of driving coherent linear processes. Better clarity to efficiently get their products to market and to support the patients that we serve. The book itself addresses the core topics that industry and regulators have struggled with, that have generated a lot of questions, and for which the regulatory expectations and best practices have come into better focus. Throughout the chapters in the book, and Barr references each as he walks through his thoughts about this, it explains where there are still questions that remain, that might warrant further policy attention, and where there might be a need for some proactive case-by-case discussions of the products with regulators, to help drive that forward motion.

Even since authoring the book and writing Chapter 1 and then the references to the other chapters within the book, each of the chapters and the things that were written in them based on feedback from Barr helped us capture the core strategies that people need to follow to be successful. The material is written in such a way that it won't go stale. The information is still valid even as new guidance comes out. Where there is a need for new policy or more clarification, like on cross-label combination products, that's called out within the book. Barr recognizes that as he walks through what he's written about in Chapter 1.

As we wrap up the conversation on Chapter 1 of The Combination Products Handbook, I want to remind the audience that I recently did an interview on another series I host called Sit and Deliver with John “Barr” Weiner, the author of Chapter 1. I encourage folks to check that out.

Susan, I want to thank you for joining me again, and I look forward to having you join me for the discussion of Chapter 2, which you authored. That chapter is called, “What is a Combination Product?” We will pick up the conversation in the episode on that particular chapter. Before we break for today, could you remind the audience where they can purchase The Combination Products Handbook: A Practical Guide?

They can find it either on routledge.com or Amazon. It’s available both in e-copy and hard copy.

Excellent. So long, folks. We will see you on the next episode of The Combination Products Handbook: The Series